THE ROLE OF CYTOCHROME P450 ISOFORMS OF HEPATOCYTE ENDOPLASMIC RETICULUM IN ETHANOL METABOLISM

I. P. Sutsko, I. Semenenya, A. Shlyahtun
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Abstract

Background. Three metabolic pathways that can function simultaneously are known to be involved in ethanol oxidation in the liver: alcohol dehydrogenase pathway, microsomal ethanol-oxidizing system, and catalase pathway. Though the cytochrome P450-dependent microsomal ethanol-oxidizing system plays an insignificant role in metabolism of small amounts of ethanol, it is induced in case of ethanol excess and becomes essential when ethanol is abused. The main components of this system are cytochrome P450 (CYP) isoforms of smooth endoplasmic reticulum. Objective. To characterize the role of the key isoforms of cytochrome P450 in ethanol oxidation. Material and methods. We carried out an analysis of modern literature data on the role of the main isoforms of cytochrome P450 in liver metabolism of ethanol. Results. Data on the primary role of cytochrome CYP2E1 in ethanol metabolism, as well as on the contribution of isoforms CYP1A2, CYP2B1/2, CYP2C, CYP3A4, CYP4B1 to ethanol oxidation are presented. Conclusions. Ethanol is metabolized by many CYPs of endoplasmic reticulum of hepatocytes. The importance of CYP in biotransformation processes in the liver necessitates the study of the role of individual CYP isoforms in ethanol metabolism for predicting changes in the pharmacokinetics of drugs and metabolism of endogenous compounds under the influence of ethanol.
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肝细胞内质网细胞色素P450亚型在乙醇代谢中的作用
背景已知三种可以同时发挥作用的代谢途径参与肝脏中的乙醇氧化:乙醇脱氢酶途径、微粒体乙醇氧化系统和过氧化氢酶途径。尽管细胞色素P450依赖性微粒体乙醇氧化系统在少量乙醇的代谢中起着不重要的作用,但它在乙醇过量的情况下被诱导,当乙醇被滥用时变得至关重要。该系统的主要成分是滑面内质网的细胞色素P450(CYP)异构体。客观的表征细胞色素P450关键异构体在乙醇氧化中的作用。材料和方法。我们对细胞色素P450主要亚型在乙醇肝脏代谢中的作用的现代文献数据进行了分析。后果介绍了细胞色素CYP2E1在乙醇代谢中的主要作用,以及亚型CYP1A2、CYP2B1/2、CYP2C、CYP3A4、CYP4B1对乙醇氧化的贡献。结论。乙醇由肝细胞内质网的许多CYP代谢。CYP在肝脏生物转化过程中的重要性需要研究单个CYP异构体在乙醇代谢中的作用,以预测乙醇影响下药物药代动力学和内源性化合物代谢的变化。
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